[Frontiers in Bioscience 13, 284-301, January 1, 2008]
Making the heart resistant to infarction: how can we further decrease infarct size?
Renaud Tissier1, Alain Berdeaux1, Bijan Ghaleh1, Nicolas Couvreur1, Thomas Krieg2, Michael V. Cohen3,4, James M. Downey3
1INSERM, Unite 841, Creteil, F-94000 France ; Ecole Nationale Veterinaire d'Alfort, Maisons-Alfort, F-94704 France, 2 Department of Cardiology, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany, 3 Department of Physiology, University of South Alabama, College of Medicine, Mobile, AL 36688, 4 Department of Medicine, University of South Alabama, College of Medicine, Mobile, AL 36688
TABLE OF CONTENTS
Acute myocardial infarction (AMI) following coronary artery occlusion is a common cause of mortality and morbidity world-wide. Patients currently receive reperfusion therapy as the only anti-infarct intervention. A number of agents have been evaluated to further improve myocardial salvage, but until recently, none has demonstrated clear efficacy in clinical trials. A new target of cardioprotection, the Reperfusion Injury Salvage Kinase (RISK) pathway, has been proposed. These kinases are involved in mediating the cardioprotection of myocardial preconditioning and postconditioning induced by short non-lethal cycles of ischemia/reperfusion performed before (preconditioning) or just after (postconditioning) a lethal ischemic insult. Many pharmacological interventions are now available that protect the heart by activating the RISK pathway at the time of reperfusion. The present review will examine the efficacy of several strategies that have been proposed to protect the acutely ischemic myocardium including (1) those intended to directly alter adverse reperfusion events (e.g., calcium overload and free radical attack), (2) those based on activation of the RISK pathway including postconditioning, and (3) myocardial cooling.